Biomarkers for cancers responsive to modulators of hec1 activity
AssigneeTaivex Therapeutics Corporation
InventorsYu-Ling Huang, Johnson Lau
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Abstract
Contemplated compositions and methods are drawn to biomarkers and methods related to treatment of neoplastic disease with Hec1 inhibitor. Gene status and/or expression levels of Hec1(HEC), Rb(RB1), and/or p53 (TP53) may be useful as biomarkers for sensitivity to treatment with a Hec1 inhibitor. In addition, Hec 1 inhibitors may show synergistic effects when used in conjunction with cytotoxic drugs.
Claims19
A method of determining sensitivity of a neoplastic cell to a Hec1 inhibitor, comprising:
- obtaining from a patient a sample comprising a neoplastic cell or neoplastic cells;
- forming a detectable complex of at least one of Hec1, Rb, and p53, wherein the at least one of Hec1, Rb, and p53 are derived from the sample;
- using the detectable complex to determine at least one of expression level and status of at least one of Hec1, Rb, and p53 to obtain a test result;
- and
- comparing the test result with a reference result of a non-neoplastic cell that includes at least one of an expression level and a status of at least one of Hec1, Rb, and p53 of the non-neoplastic cell to thereby determine sensitivity of the neoplastic cell to the Hec1 inhibitor.
A method of evaluating a patient having a neoplastic disease for potential treatment with a Hec1 inhibitor, comprising:
- obtaining a patient sample comprising a neoplastic cell or neoplastic cells;
- forming a detectable complex of at least one of Hec1, Rb, and p53;
- using the detectable complex to determine at least one of expression level and status of at least one of Hec1, Rb, and p53 to obtain a test result;
- comparing the test result with a reference result that includes at least one of an expression level and a status of at least one of Hec1, Rb, and p53 of a non-neoplastic reference cell to thereby determine sensitivity of the neoplastic cell to the Hec1 inhibitor;
- and
- including the patient into a treatment group that receives treatment with a Hec1 inhibitor.
The method of claim 6 wherein a mutated or deleted form of the at least one of the Rb and the p53 relative to a corresponding reference result is indicative of sensitivity of the neoplastic cell to the Hec1 inhibitor.
A method of evaluating a patient having a neoplastic disease for potential treatment with a Hec1 inhibitor, comprising:
- determining from a patient sample a molecular type of the neoplastic disease;
- forming a detectable complex of at least one of Hec1, Rb, and p53;
- using the detectable complex to determine for the molecular type at least one of expression level and status of at least one of Hec1, Rb, and p53;
- using the at least one of the expression level and the status of the at least one of Hec1, Rb, and p53 to thereby provide an evaluation result;
- and
- wherein an increased expression level of Hec1 relative to a corresponding reference result and/or presence of a mutated or deleted form of the at least one of the Rb and the p53 relative to a corresponding reference result is indicative of suitability of treatment of the neoplastic disease with a Hec1 inhibitor.
The method of claim 11 wherein the neoplastic disease is breast cancer.
A method of treating a neoplastic cell that is sensitive to treatment with a Hec1 inhibitor, comprising contacting the neoplastic cell with a Hec1 inhibitor and a second chemotherapeutic agent at a dosage effective to achieve a synergistic result with respect to growth inhibition of the neoplastic cell.
The method of claim 16 wherein the Hec1 inhibitor is selected from the group consisting of N-(4-(4-isopropoxy-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (100951), N-(4-(4-(4-methoxyphenoxy)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (101001), 2-fluoro-N-(4-(4-(4-methoxyphenoxy)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (101015), N-(4-(4-(5-(2-methoxyethoxy)pyrazin-2-yloxy)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (Hec110091), N-(4-(4-(5-(2-methoxyethoxy)pyrazin-2-ylthio)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (110095), and N-(4-(4-(5-(2-(dimethylamino)ethoxy)pyrazin-2-ylthio)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide, and their salt forms.
A method of treating a neoplastic cell that is multi-drug resistant or resistant to treatment with imatinib, comprising contacting the neoplastic cell with a Hec1 inhibitor and optionally a second chemotherapeutic agent at a dosage effective to achieve growth inhibition of the neoplastic cell.
The method of claim 19 wherein the Hec1 inhibitor is selected from the group consisting of N-(4-(4-isopropoxy-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (Hec100951), N-(4-(4-(4-methoxyphenoxy)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (Hec101001), 2-fluoro-N-(4-(4-(4-methoxyphenoxy)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (Hec101015), N-(4-(4-(5-(2-methoxyethoxy)pyrazin-2-yloxy)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (Hec110091), N-(4-(4-(5-(2-methoxyethoxy)pyrazin-2-ylthio)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (Hec110095), and N-(4-(4-(5-(2-(dimethylamino)ethoxy)pyrazin-2-ylthio)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide or its salt forms.
Dependencies are inferred from the claim text.